DOWN-REGULATION OF NUCLEAR-BINDING ACTIVITIES OF OXBOX-REBOX TRANSCRIPTION FACTORS DURING CELLULAR SENESCENCE

Functional capacity of mitochondria declines during aging and this imp airment may have a major role in aging process. Several observations i ndicate that transcriptional efficiency is reduced during aging. Our p urpose was to find out whether aging and cellular senescence affect th e nuclear binding activities of transcription factors which bind to OX BOX-REBOX sequence present in promoter regions of numerous nuclear gen es encoding mitochondrial proteins. These factors regulate and coordin ate the expression of mitochondrial proteins. We observed a strong dow n-regulation in the nuclear binding activities of OXBOX-REBOX factors in replicatively senesced human WI-38 and IMR-90 fibroblasts. On the c ontrary, SV-40 immortalization highly increased the nuclear binding ac tivities. A considerable down-regulation of OXBOX-REBOX factors was al so observed in UVB-irradiated WI-38 fibroblasts. Irradiation induced p hotoaging in fibroblasts which involved cell cycle arrest and senescen t morphology. Interestingly, the nuclear binding activities of OXBOX-R EBOX factors were also prominently decreased in the liver of Wistar ra ts at the age of 30 months but not yet at the age of 18 months. Our re sults suggest that the down-regulation of OXBOX-REBOX factors could af fect the expression level of mitochondrial proteins encoded in nucleus and hence induce disturbances in mitochondrial function and promote t he cellular aging process. (C) 1996 Academic Press, Inc.